Ketamine-induced hepatoprotection: the role of heme oxygenase-1
AUTOR(ES)
Suliburk, James W.
FONTE
American Physiological Society
RESUMO
Lipopolysaccharide (LPS) causes hepatic injury that is mediated, in part, by upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Ketamine has been shown to prevent these effects. Because upregulation of heme oxygenase-1 (HO-1) has hepatoprotective effects, as does carbon monoxide (CO), an end product of the HO-1 catalytic reaction, we examined the effects of HO-1 inhibition on ketamine-induced hepatoprotection and assessed whether CO could attenuate LPS-induced hepatic injury. One group of rats received ketamine (70 mg/kg ip) or saline concurrently with either the HO-1 inhibitor tin protoporphyrin IX (50 μmol/kg ip) or saline. Another group of rats received inhalational CO (250 ppm over 1 h) or room air. All rats were given LPS (20 mg/kg ip) or saline 1 h later and euthanized 5 h after LPS or saline. Liver was collected for iNOS, COX-2, and HO-1 (Western blot), NF-κB and PPAR-γ analysis (EMSA), and iNOS and COX-2 mRNA analysis (RT-PCR). Serum was collected to measure alanine aminotransferase as an index of hepatocellular injury. HO-1 inhibition attenuated ketamine-induced hepatoprotection and downregulation of iNOS and COX-2 protein. CO prevented LPS-induced hepatic injury and upregulation of iNOS and COX-2 proteins. Although CO abolished the ability of LPS to diminish PPAR-γ activity, it enhanced NF-κB activity. These data suggest that the hepatoprotective effects of ketamine are mediated primarily by HO-1 and its end product CO.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2697945Documentos Relacionados
- Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL.
- Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival
- Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene
- Heme oxygenase-1 and carbon monoxide in pulmonary medicine
- Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury